Our program Project is dedicated to studying human breast cancer in vivo. This often means that biological studies are performed directly on clinical specimens. This can be problematic when assessing the structure and expression of genes, in that clinical specimens are nearly always composed of complex mixtures of normal cells and tumor cells. The results of the extremely sensitive molecular techniques we use to analyze DNA and RNA are uninterpretable unless their substrate is prepared from a highly purified sample of one cell type. Thus, target cells must be separated from non-target cells before the samples are prepared, and we do this by manually microdissecting histological tissue sections on glass slides. Several of these molecular techniques (e.g. allelic imbalance, single-strand conformational polymorphism, differential display, and reverse-transcriptase PCR) are being used by three projects in this Program Project (projects 3, 4, and 5). The samples supporting these studies will come from the Evolutionary Tissue Bank in the Tumor Bank and Data Network Core, and the slides will be prepared in the Histology and Immunohistochemistry Core. They will be microdissected in this Core.